微生物与感染
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2021 Vol.16 No.5
Published 2021-10-25
Invited paper
Original Article
Case Analysis
Review
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Original Article
298
SONG Jieyu1, SHAN Pu2, LI Shuxiang2, QIU Chao1, XU Jing2, WANG Xuanyi1, 3, WEN Yumei1
Impact of antigen-antibody immune complex vaccine on decline of serum hepatitis B virus surface antigen levels in chronic hepatitis B patients
For chronic hepatitis B (CHB) therapy, a new concept named “functional cure” that is defined as loss of the serum hepatitis B virus surface antigen (HBsAg) is proposed and pursued clinically in recent years. However, this goal is hard to be approached by current available antiviral therapy. To understand the performance on reduction of HBsAg in antigen-antibody complex therapeutic hepatitis B vaccine (YIC)-treated CHB patients, a pooled analysis was carried out based on phase Ⅱb and Ⅲb trials. After treatment and withdrawal follow-up, it showed that those who achieved HBV e antigen (HBeAg) seroconversion experienced a decrease of HBsAg level up to 0.95log
10
IU/mL, which was significantly higher than 0.32log
10
IU/mL of those who did not achieve HBeAg seroconversion (
P
<0.01). Conversely, the reduction was 0.49log
10
IU/mLand 0.36log
10
IU/mL among HBeAg seroconverted and non-converted patients in control group treated with aluminum hydroxide adjuvant (Alum). During treatment period, alanine aminotransferase (ALT) flare was more frequently detected among those patients who reached a HBsAg reduction of >1.0log
10
IU/mL in YIC group, rather than in Alum group. Predictors of HBsAg reduction were HBeAg seroconversion, B genotype of HBV infection, ALT flare occurred during treatment, and high serum HBsAg levels at baseline. Since specific adaptive immune response elicited by YIC has been demonstrated in some CHB patients, to further improve the rate of “functional cure”, the “sandwich” strategy (antiviral treatment + HBsAg monoclonal antibody + YIC) might be considerable.
2021 Vol. 16 (5): 298-303 [
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304
TANG Jiayi, CAI Yanxing, Wang Xinling, JIANG Shibo, LU Lu
The establishment and application of an ASFV pseudovirus infection cell model
African swine fever virus (ASFV) poses a serious threat to animal health, food safety, and even the global economy. To date, there is still no ASFV vaccine or therapeutic available. For biosafety reasons, most researches on ASFV must be conducted in biosafety level 3 (BSL-3) laboratories. This is the main obstacle for the study on ASFV, including its pathogenesis and escape mechanism, and the development of ASFV vaccines and therapeutics. In this study, we selected some ASFV envelope proteins that are reported to participate in the process of viral entry into the host cell and used the vesicular stomatitis virus (VSV) pseudovirus packaging system to produce several ASFV pseudoviruses. We found that one of these ASFV pseudoviruses could effectively infect some ASFV-susceptible cells, and thus established an ASFV pseudovirus infection cell model, which could be used in laboratories with a lower biosecurity level. As the pseudovirus contains a Renilla luciferase reporter gene, this ASFV pseudovirus could be used for screening of ASFV entry inhibitors and neutralizing antibodies, thus providing a safe and convenient model for research and development of antiviral drugs against ASFV infection.
2021 Vol. 16 (5): 304-312 [
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313
HU Kongying, JIN Yutao, YE Jianyu, ZAI Wenjing, WANG Yang, LI Yumeng, CHEN Jieliang
Comparison of two methods for extracting hepatitis B virus covalently closed circular DNA
Hepatitis B virus (HBV) is a hepatotropic DNA virus that can deposit a covalently closed circular DNA form (cccDNA) in the nucleus of infected hepatocytes, which serves as a reservoir for HBV genome and the template for transcribing HBV RNAs. The persistence of cccDNA is the key of HBV chronicity and the main obstacle for HBV cure, and thus cccDNA has always been a focus of HBV research. The efficient extraction of cccDNA from cells is required for accurate detection and quantification. Hirt DNA extraction is a method for isolation of the extrachromosomal DNA in eukaryotes and has been applied for cccDNA extraction. However, the procedure of Hirt DNA extraction is laborious and time-consuming. To simplify the procedure, there has been reports of ”modified Hirt DNA extraction” combined with silicon-based resins column for rapid extraction of extrachromosomal DNA. However, the difference of extraction efficacy between the two methods remains unknown. Here, the two methods were parallelly compared by using Southern Blot and qPCR in various cell culture-based HBV transfection, replication and infection systems. The results suggested that “the modified Hirt-Silica Gel Membrane method” has the potential to enable a fast HBV cccDNA extraction with equally extraction efficacy and specificity compared with “the original Hirt-Phenol/Chloroform method”.
2021 Vol. 16 (5): 313-321 [
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322
TANG Xiaoli1, WEI Junbin2, FENG Yi3, LE Ning3, LIANG Danna4, ZHUO Shaoyuan3, SHANG Liguo3
Chlorogenic acid represses biofilm formation of Pseudomonas aeruginosa via increasing RsmA expression
Pseudomonas aeruginosa
(
P. aeruginosa
) is a common human opportunistic pathogen, and the biofilm formation could enhance its antibiotic tolerance. Chlorogenic acid (CA) has been reported to repress the biofilm formation of
P. aeruginosa
, so the present study aims to further explore the regulatory mechanism of CA, especially the effect of CA on the expression of Gac-Rsm (global secondary metabolism regulation system). The results showed that CA could repress the biofilm formation of
P. aeruginosa
, reduce exopolysaccharide production, although the transcription level of
pslA
(synthetase gene of key exopolysaccharide psl) was not significantly changed. The expression of RsmA (core regulator in Gac-Rsm system) was enhanced and the level of key signal molecule cyclic dimeric guanosine monophosphate (c-di-GMP) was reduced. It is suggested that CA represses the biofilm formation of
P. aeruginosa
via increasing the expression of RsmA.
2021 Vol. 16 (5): 322-330 [
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331
LI Fei1, ZHU Qiguo2, SHI Peng3, CAO Lingfen4, WANG Libo5, LU Roujian6, TAN Wenjie6, SHEN Jun1
Etiological analysis of pulmonary alveolar lavage fluid in hospitalized children with consolidated pneumonia
The purpose of this study is to analyze the pathogenic spectrum of children’s pneumonia with pulmonary consolidation, and provide information for clinical empirical anti-infection treatment. From January 2019 to January 2020, the clinical data of hospitalized children with pneumonia diagnosed who underwent fiberoptic bronchoscopy in our center were retrospectively reviewed. By the reading of two senior pediatric infectious doctors, the data of pathogens detection result of bronchoalveolar lavage fluid (BALF) from children with pneumonia and/or pulmonary consolidation were analyzed. The diagnosis of lung consolidation was based on imaging evidence. 286 BALF samples from 286 children with mean age of 5.5 (5.8±3.1) years were detected. 195 cases (68.2%) with pulmonary consolidation. The positive detection rates of pathogens in all patients were 76.6% (219/286). The positive detection rates of patients with or without pulmonary consolidation were 77.9%(152/195)and 73.6%(67/91)respectively (
P
>0.05). Mycoplasma pneumoniae, adenovirus, rhinovirus, respiratory syncytial virus and parainfluenza virus type 3 were the top five detected pathogens. Mycoplasma pneumoniae got the highest positive rate 77.0%(127/165)in children of 5 years old and above. The detection rates of mycoplasma pneumoniae in patients with or without pulmonary consolidation were 67.2% (131/195) and 61.5% (56/91), respectively, (
P
>0.05). Mycoplasma pneumoniae, adenovirus, rhinovirus, respiratory syncytial virus and parainfluenza virus type 3 infection were the dominant etiology of children’s pneumonia in the target population. The pathogens detection rates were similar in patients with or without pulmonary consolidation.
2021 Vol. 16 (5): 331-338 [
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Case Analysis
339
REN Wei, LIU Li, Xie Guangqing, LONG Xiaoling
Clinical features of 3 cases of infants with
Elizabethkingia meningoseptica
meningitis
To summarize the clinical features of
Elizabethkingia meningoseptica
(EM) meningitis in infants. Case histories (including clinical features, laboratory examination, treatment, prognosis) of 3 EM meningitis in infants who were hospitalized at Boai Hospital from January 1, 2010 to December 31, 2020 were analyzed retrospectively. 3 cases were diagnosed by a positive cerebrospinal fluid culture of EM. 3 cases were full-term natural delivery, 2 cases were neonatal onset, 1 case was 35 days onset, no risk factors were found before onset. Fever was the main symptom, no convulsions and meningeal irritation sign. Peripheral blood leucocyte count, C-reactive protein and procalcitonin of 3 cases were increased. Pan's test of cerebrospinal fluid (CSF) was positive, the nucleated cell count in CSF was elevated; the protein level was substantially elevated; the glucose level was decreased. Representation of CT or MRI examination showed meningeal enhancement, without brain parenchyma involvement. The results of drug sensitivity of 3 strains showed high consistency. Drug sensitivity test showed that bacteria were all sensitive to ciprofloxacin, piperacillin/tazobactam, levofloxacin and cotrimoxazole. 2 cases were treated with ciprofloxacin, 1 case was treated with meropenem combined with vancomycin, one case was cured, and two cases were discharged after clinical improvement. Telephone follow-up showed that the general condition of 3 cases was normal. EM meningitis mainly occurs in the neonatal stage, fever was the main manifestation. EM was resistant to the antimicrobials which had been commonly used in the department of pediatrics in vitro and sensitive to quinolones.
2021 Vol. 16 (5): 339-342 [
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343
MIN Yan, WU Jing, LI Jixia, HU Chengjin
A case of brain abscess caused by
Streptococcus constellatus
This paper reports a case of brain abscess caused by
Streptococcus constellatus
. The patient, a 54-years-old male with double vision for 19 days, was treated with anti-tuberculous therapy based on nuclear magnetic resonance imaging (MRI) findings that did not exclude the formation of tuberculosis balls from tuberculosis infection. Metagenomic sequencing of the cerebrospinal fluid was also performed, and the results showed that
Campylobacter recti
and
Fosetylastanella
were the main causative organisms. On follow-up history, the patient had periodontal disease and recent significant left-sided maxillary pain. After reviewing the literature, there were reports of intracranial abscesses caused by
Campylobacter recti
, so anti-tuberculosis treatment was stopped and moxifloxacin antibacterial therapy was used instead. The patient's headache and discomfort worsened, and the MRI was repeated again, suggesting gradual expansion of the lesion and rapid change of the condition, and the cerebellar occupying lesion was removed urgently. Brain abscess with tissue culture resulted of
Streptococcus constellatus
. The patient was discharged from the hospital in stable condition after comprehensive treatment with linezolid anti-infective therapy according to drug sensitivity.
2021 Vol. 16 (5): 343-346 [
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Review
347
WANG Yuli1, LIU Chang1, NIU Chen1, WU Jian1,2,3
The mechanism of intestinal dysbiosis affecting nonalcoholic fatty liver disease and its intervention strategies
Incidence of nonalcoholic fatty liver disease (NAFLD) has been increasing, and NAFLD has become one of the most common liver diseases. Its pathogenesis has not been fully elucidated, and there are no effective medications so far. As the ‘second genome’ of human body, gut microbiota plays an important role in nutrient digestion, absorption and metabolism. Growing evidence has suggested that gut dysbiosis contributes significantly to occurrence of NAFLD and is critical for progression of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), liver fibrosis or hepatocellular carcinoma (HCC). Therefore, new strategies for gut microbiota intervention are developed to prevent or treat NAFLD. This review intends to mainly discuss the impacts of intestinal microbial abnormality on the pathogenesis, mechanism and intervention of NAFLD/NASH.
2021 Vol. 16 (5): 347-355 [
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356
DONG Kedi, ZHU Yuan, DENG Qifeng, WU Shuyan, HUANG Rui
Research progress of necroptosis in bacteria-host interactions
Necroptosis is one of the regulated cell death mediated by receptor-interacting protein (kinase) (RIP/RIPK). It can be divided into the classical pathway that depends on RIPK1 and the non-classical pathway which is independent of RIPK1. RIPK3 and mixed lineage kinase domain-like (MLKL) are activated orderly through the above two ways, and finally induce necroptosis. With in-depth research, there are many forms of cell death have been discovered in the process of pathogenic microorganism infection. Pathogenic microorganisms cause various forms of cell death in the process of infection and the outcome of infection is highly dependent on the fate of cells. On the one hand, bacterial virulence factors cause lead to necroptosis of host cells; on the other hand, necroptosis is also an important way of host immune defense. It is of great significance to explore the interaction between bacteria and host for revealing the occurrence and development of infectious diseases.
2021 Vol. 16 (5): 356-362 [
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363
MA Jiaye, XU Jinchuan, YAN Bo, LU Shuihua
Progress in animal models of latent tuberculosis infection
Latent tuberculosis infection (LTBI) is a state of persistent immune response to
Mycobacterium tuberculosis
antigen without clinical symptoms or imaging findings of active tuberculosis. The relapse of LTBI is one of the main sources of active tuberculosis. Generating an LTBI animal model is the foundation for studying mechanisms of latency and recurrence of tuberculosis infection, developing diagnostic reagents, and assessing the efficacy and safety about new anti-tuberculosis drugs and vaccines. Developing an LTBI animal model with consistent phenotype, low cost, easy to master and popularize, suitable length of time of latent period, small variation in relapse threshold and relapse level would be the future direction for LTBI related studies. This review summarizes the researches on animal models of LTBI, with the hope of providing reference for those who are engaged in tuberculosis control.
2021 Vol. 16 (5): 363-372 [
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